Cadonilimab for PD-1/PD-L1 Blockade-refractory, MSI-H/dMMR, Advanced Colorectal Cancer

May 20, 2026 updated by: Yanhong Deng, Sun Yat-sen University

Cadonilimab (Bispecific Anti-PD-1/CTLA-4 Antibody) for PD-1/PD-L1 Blockade-refractory, Microsatellite Instability-high (MSI-H) or Mismatch Repair-deficient (dMMR), Advanced Colorectal Cancer: a Single Group, Multicenter, Phase 2 Trial

KEYNOTE-177 is currently the only randomized controlled phase III clinical trial evaluating the efficacy and safety of pembrolizumab versus standard chemotherapy combined with targeted first-line therapy for dMMR/MSI-H metastatic colorectal cancer. The study was conducted at 192 centers in 23 countries and enrolled a total of 307 subjects. The results of the study showed that the median PFS of pembrolizumab was 16.5 months, which was double the 8.2 months in the chemotherapy group (HR 0.60; 95% CI: 0.45-0.80; P = 0.0002). In addition, the ORR was 45.1% in the pembrolizumab group and 33.1% in the chemotherapy group, and a higher percentage of patients achieving a complete remission (CR) with pembrolizumab than in the chemotherapy group (13.1% vs. 3.9%). The U.S. FDA approved pembrolizumab in June 2020 for the first-line treatment of MSI-H/dMMR metastatic colorectal cancer.

The results of the KEYNOTE-177 study showed that 29% of patients with dMMR/MSI-H metastatic colorectal cancer experienced direct disease progression (PD) after first-line pembrolizumab monotherapy. This may suggest that some dMMR/MSI-H patients have primary resistance to anti-PD-1 monotherapy. In the first-line treatment cohort of the CheckMate 142 study using nivolumab combined with ipilimumab, the proportion of patients with direct PD was 13%, suggesting that the combination of PD-1 inhibitors and anti-CTLA-4 mAb may have help overcome this primary resistance. In addition, in the second-line and above cohort of the CheckMate142 study, 12% of patients receiving nivolumab in combination with ipilimumab experienced PD directly, compared with 26% of patients receiving nivolumab alone.

A study published on 《The Lancet Oncolog》 on the efficacy and safety of ipilimumab monotherapy and ipilimumab combined with anti-PD-1 monoclonal antibody in patients with anti-PD-1 monoclonal antibody-resistant melanoma Retrospective study. The study included 355 patients with unresectable metastatic stage III or IV melanoma who received ipilimumab monotherapy after failure of anti-PD-(L)1 monoclonal antibody (n=162), or Ipilimumab combined with anti-PD-1 therapy (n=193). The ORR was 31% in the combination arm, significantly higher than the 13% in the ipilimumab monotherapy arm. In addition, the median OS and PFS of the combination therapy group were 20.4 months and 3.0 months, respectively, which were also significantly higher than those of the single-agent group of 8.8 months and 2.6 months.

The aim of this study was to evaluate the objective response rate (ORR) of Cadonilimab, a bispecific anti-PD-1/CTLA-4 antibody, for PD-1/PD-L1 blockade-refractory, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), advanced colorectal cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Qin Zheng

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510655
        • Recruiting
        • The sixth affiliated hospital of Sun Yat-Sen University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Willing and able to provide written informed consent.
  2. Histological or cytological documentation of adenocarcinoma of the colon or rectum.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  4. Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
  5. Subjects with stage IV colorectal cancer must have measurable or non measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.
  6. Previous treatment with an anti-PD-1 or PD-L1 monoclonal antibody for advanced or metastatic colorectal cancer has failed. Treatment failure was defined as: disease progression or unacceptable toxicity during treatment or within 6 months after the last treatment.
  7. Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol.

Exclusion Criteria:

  1. Previously received anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody.
  2. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
  3. Heart failure grade III/IV (NYHA-classification).
  4. Unresolved toxicity higher than CTCAE v.5.0 Grade 1 attributed to any prior therapy/procedure.
  5. Subjects with known allergy to the study drugs or to any of its excipients.
  6. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
  7. Breast- feeding or pregnant women.
  8. Lack of effective contraception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cadonilimab
Cadonilimab alone
Drug: Cadonilimab
Cadonilimab, 6 mg/kg every 2 weeks until disease progression, intolerable toxicity, or duration of treatment for 2 years

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
12-month Progression-free survival (PFS) rate
Time Frame: 2 years
The PFS was defined as the time from enrollment until tumor progression or death from any cause, whichever occurred first. The 12-month PFS rate was defined as the proportion of patients without disease progression or death at the 12th month after initiation of the study. treatment.
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 2 years
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR).
2 years
Overall Survival (OS)
Time Frame: 5 years
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
5 years
Toxicity assessed using the The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time Frame: 2 years
The grade of toxicity will be assessed using the NCI-CTCAE, version 5.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 (lowest level) through 5 (highest level) with unique clinical descriptions of severity.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 7, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 21, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CSWOG-C03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colorectal Cancer Stage IV

Clinical Trials on Cadonilimab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings